This invention relates to a process for preparing .alpha.-phenylpropionic acid on an industrial scale.
.alpha.-Phenylpropionic acid, which exhibits various pharmacological effects including analgesic, anti-inflammatory and antipyretic ones, is useful as a medicine.
Recently there have been proposed a number of pathways for synthesizing .alpha.-phenylpropionic acid. For example, there have been attempted some processes for preparing .alpha.-phenylpropionic acid in a single step by reacting an .alpha.-phenylethyl alcohol derivative or a styrene derivative with carbon monoxide.
Japanese Patent Laid-Open No. 10545/1984 discloses a process for preparing .alpha.-phenylpropionic acid from a styrene derivative with the use of a palladium complex as a catalyst. In spite of the high yield, this process is inferior to a process wherein an .alpha.-phenylethyl alcohol derivative is directly carbonylated, since the styrene derivative should be prepared through dehydration of an .alpha.-phenylethyl alcohol derivative wherein the high polymerization activity of the styrene derivative results in a poor dehydration yield.
Regarding the direct carbonylation of an .alpha.-phenylethyl alcohol derivative, it is known that a palladium complex catalyst is effective in carbonylating .alpha.-(alkoxyphenyl)ethyl alcohol but is useless for other .alpha.-phenylethyl alcohol derivatives (cf. Japanese Patent Laid-Open No. 95238/1984). Further there has been reported a process for carbonylating an .alpha.-phenylethyl alcohol derivative with the use of a cobalt or rhodium complex in the presence of water (cf. Japanese Patent Laid-Open No. 97930/1977). However this process seems hardly effective, since no .alpha.-phenylpropionic acid was prepared in our follow-up examination thereof (cf. Comparative Example 1).
On the other hand, there is known a process for preparing a carboxylic acid not from an .alpha.-phenylethyl alcohol derivative but from a common alcohol with the use of rhodium and an iodine compound as catalysts (cf. Japanese Patent Publication No. 3334/1972). When this process is applied to a process for preparing .alpha.-phenylpropionic acid from an .alpha.-phenylethyl alcohol derivative, which is to be carried out at such a high concentration of the iodine compound and a high reaction temperature as will be described in Examples hereinafter, however, the extremely high polymerization activity of said derivative results in the formation of a large amount of a polymer as a by-product and thus the desired .alpha.-phenylpropionic acid can be hardly obtained (cf. Comparative Example 2).